ABSTRACT ? Imaging Management and Analysis Core The Imaging Management and Analysis Core (Imaging Core) will meet the requirements of the three Measuring, Modeling, and Controlling Heterogeneity-Cancer Systems Biology Consortium (M2CH-CSBC) Projects and the Outreach Core by developing and integrating state-of-the-art resources for a complete imaging workflow. Specifically, we will 1) use high-content imaging to measure baseline and drug and microenvironment response phenotypes separately and in combination in a panel of cell lines, 2) optimize and deploy novel, highly multiparameter cyclic multiplexed immunofluorescence (cmIF) imaging workflows to measure microenvironment and drug responses in heterogeneous tissues in 2D and 3D, and 3) deploy correlative light/electron microscopic analysis based on super-resolution light microscopy and scanning electron microscopy to provide the ultrastructural cellular context. To execute these tasks in close collaboration with the Projects, the Imaging Core will expand on existing resources and build a customized imaging environment to a) acquire image data in automated ways from the multiple imaging instruments, following precise protocols and maintaining complete metadata, b) store images and metadata and all derived and associated measurement data in highly robust databases and repositories with powerful query, visualization, and programmer access tools, c) quantitatively analyze images by deploying and developing state-of-the-art image reconstruction methods, image segmentation algorithms, feature extraction and classification routines, normalization procedures, and machine learning approaches to classify image features at multiple resolution levels, and d) develop novel visualization methods for interacting with images and extracted features and models in combination with experimental metadata and data from external databases.